8. Trimeric G Protein Signaling Flashcards
what are the 2 things required to stimulated adenylyl cyclase?
hormone (ligand) & GTP
2 major signaling mechanisms that a cell can use?
- direct phosphorylation
2. signaling via nucleotide-triphosphate-binding to a G protein
GTPase enzyme kinetics
has a low Km (high affinity)
3 subunits of G proteins?
alpha
beta
gamma
G-as
defines the majority of G protein function
activates AC
G-aq
activates PLC-beta
What is the rate limiting step for a reaction with a G protein?
dissociation of GDP from the alpha subunit
G protein, by default, is in what form?
OFF (T-form)
second step proceeds 10x faster when a ligand is not bound to the GPCR
example of G protein signaling: epinephrine
E binds receptor
GDP dissociates, replaced by GTP, activates Gas
Gas activates AC
AC catalyzes formation of cAMP
cAMP activates PKA
PKA phosphorylates cellular proteins that cause the cellular response to E
GPCR structure
7 transmembrane domains
which cytoplasmic loop interacts with the G protein the most?
3rd
receptor is buried within the membrane
what does AC do?
catalyze the formation of cAMP
What does PLC do?
break PIP2 into IP3 & DAG
What activates PLPC-beta
G-alpha-q
Secondary messengers examples (4)
cAMP
IP3
DAG
Calcium
what does cAMP do?
acts as a secondary messenger to protein kinases i.e. cAMP dependent protein kinase
what does IP3 do?
release calcium from ER stores
What does DAG do?
activates PKC
calmodulin structure? and what does it do?
4-calcium holding protein, enables safe Ca storage & quick Ca release
activates Ca calmodulin dependent kinase
what do multifunctional kinases do?
pass and amplify signal
what do tyrosine kinases do?
deliver signal to its target destination
PKA strucutre?
2 regulatory subunits
2 catalytic subunits
how does cAMP activate PKA?
2 cAMPs per regulatory subunit, bind to substrate sites, causing regulatory subunits to dissociate from the catalytic subunits–conformational change to the catalytic subunits to make them active and ready to find proteins
what does PKC do?
controls phosphorylation of certain serine and threonine residues on select proteins and eventually elicit a cellular response
CAMK II
serine/threonine protein kinase
integral in the learning process
as the frequency of calcium waves increases within a cell, what happens to CAM KII?
more units of CAM KII are activated, increasing the overall activity of CAM KII
